We have continued to study the efficacy of daily low dose cyclophosphamide and prednisone as remission-inducing and potentially curative therapy in systemic vasculitis. The long-term toxicity of daily cyclophosphamide therapy in some patients has led to studies of alternative treatment including (1) intermittent intravenous high dose cyclophosphamide, and (i)- weekly low dose methotrexate in each of the systemic vasculitides, and (3) daily trimethoprim/sulfamethoxazole in limited Wegener's granulomatosis. A prospective analysis of bronchoalveolar lavage in Wegener's granulomatosis and controls has demonstrated that disease exacerbations are characterized by neutrophilic alveolitis, macrophage-leukocyte phagocytosis and the production of anti-neutrophil cytoplasmic antibodies in the lung. These observations suggest that neutrophilic inflammation and abnormal immune reactivity to neutrophil antigens may play a role in the pathogenesis of this disease. The pathogenesis of the vasculitides is also being investigated in vitro with the aid of endothelial cell systems to (1) characterize leukocyte binding to normal control and autologous endothelial cells, (2) assess antibody reactivity and serum cytotoxicity to normal and autologous endothelial cells, and (3) determine whether sex hormones influence leukocyte-endothelial cell adhesion, a question that is particularly relevant to Takayasu's arteritis. An epidemiologic analysis of patients with Wegener's granulomatosis has continued to evaluate environmental factors, such as inhalant exposures and patient clusters.